medwireNews: Adjuvant pembrolizumab significantly improves recurrence-free survival, compared with placebo, when given to patients with high-risk stage III melanoma for up to 1 year, researchers report in The New England Journal of Medicine.
The phase III KEYNOTE-054 study, which was also presented at the American Association for Cancer Research Annual Meeting 2018, held in Chicago, Illinois, USA, included over 1000 patients with completely resected stage III melanoma.
The patients were randomly assigned to receive intravenous pembrolizumab 200 mg (n=514) or placebo (n=505) every 3 weeks for a total of 18 doses (approximately 1 year), or until disease recurrence or unacceptable toxicity occurred.
At 1-year, the recurrence-free survival (RFS) rate was significantly higher among the patients receiving pembrolizumab than among those receiving placebo, at 75.4% versus 61.0%, giving a hazard ratio (HR) of 0.57. And the rate remained higher at 18 months (71.4 vs 53.2%).
Similar results were observed in a subgroup of 853 patients with PD-L1–positive tumors for whom the 1-year RFS rates were 77.1% and 62.6% (HR=0.54) with pembrolizumab and placebo, respectively.
Patients with PD-L1–negative tumors also significantly benefitted from pembrolizumab treatment, with 1-year RFS rates of 72.2% among the 59 patients who received pembrolizumab and 52.2% among the 57 patients who received placebo (HR=0.47).
Further subgroup analyses showed that the benefits of pembrolizumab occurred across stage IIIA, B, and C disease, and regardless of BRAF mutation status.
Specifically, patients with stage IIIA melanoma who received pembrolizumab had a nonsignificant 62% lower risk for recurrence or death at 1-year than did those who received placebo. The corresponding risk reductions were a significant 42% for patients with stage IIIB and IIIC disease, 39% for patients with wild type BRAF, and 41% for those with V600E or V600K BRAF mutations.
Alexander Eggermont (University of Paris-Saclay, Villejuif, France) and co-investigators also report that they observed no new toxic effects and that the rate of pembrolizumab-related grade 3 to 5 adverse events (14.7%) was similar to that observed with nivolumab (14.4%) in previous studies and lower than that observed with ipilimumab (45.9%).
The incidence of grade 3 or 4 immune-related adverse events was also low (7.1% and 0.6%, respectively), with 34 of 36 cases resolving within 2 months of the last dose of pembrolizumab. There was, however, one treatment-related death due to myositis in the pembrolizumab group.
Eggermont and co-authors conclude that their data “provide more evidence that drugs that are effective in advanced melanoma also have effectiveness as adjuvant therapy.”
They add that the trial “will continue to its secondary end points, distant metastasis-free survival and overall survival.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group